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Danon DiseasePhase 1NCT03882437

Gene Therapy for Male Patients With Danon Disease (DD) Using RP-A501; AAV9.LAMP2B

A Phase 1 study testing RP-A501 in people with Danon Disease, run by Rocket Pharmaceuticals Inc. at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a non-randomized open-label Phase 1 study to evaluate the safety and toxicity of gene therapy using a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon… Read more about this study

Who is it for?
Ages 8 years and older, men only
Conditions the study is for
Danon Disease
What is being tested?
RP-A501
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
7 participants
Where
3 sitesUnited States
Study dates
17 Apr 2019to 3 Jul 2025
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 years and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Main Criteria for Inclusion:

The study will enroll adult and pediatric males with a confirmed diagnosis of DD. Patients may be of any race or ethnicity. Patients and/or competent custodial parents must provide informed written consent and meet all of the enrollment criteria as detailed subsequently to be eligible to participate.

  1. DD diagnosis with any confirmed LAMP2 mutation(s).
  2. Cardiac involvement as documented by at least one abnormal finding on electrocardiogram (ECG), echocardiogram, gadolinium-enhanced cardiac magnetic resonance imaging (MRI), or electrophysiology study.
  3. Age ≥15 years for cohorts 1 and 2; 8-14 years for cohorts 1A.
  4. Male gender.
  5. New York Heart Association (NYHA) Class II or III.
  6. Adequate hematologic function as defined by hemoglobin, absolute neutrophil count (ANC), and platelet count ≥ lower limit of normal (LLN).
  7. Adequate hepatic function as defined by:
  8. AST and ALT ≤10.0×ULN or GGT ≤2.0×ULN (transaminase elevations in DD are considered extensively to result from muscle injury; hence the relatively high upper limit for transaminases and consideration of GGT level, and the presence of additional hepatic eligibility markers of bilirubin and PT/INR).
  9. Serum bilirubin ≤1.2×ULN (i.e., Grade ≤1 bilirubin increase).
  10. PT/INR ≤1.2×ULN (in the absence of anticoagulation).
  11. Absence of cirrhosis or other signs of inflammation on liver ultrasound
  12. Adequate renal function as defined by creatinine ≤ULN.
  13. Ability to provide informed consent (for adult patients and parents/legal guardians of pediatric patients) and assent (for patients age 15-17).
  14. Ability to comply with study procedures including investigational therapy and follow-up evaluations.
  15. Able to walk >150 meters unassisted during the 6MWT.
  16. Patient has received meningococcal vaccination recommended by Centers for Disease Control as appropriate for age and health condition (vaccination must be performed at least 6 weeks prior to IP administration).

Main Criteria of Exclusion:

Patients meeting any of the following criteria are not eligible for study participation:

  1. I.V. therapy with positive inotropes, vasodilators, or diuretics within the 30 days prior to enrollment (i.e., patient must be stable on oral medical therapy).
  2. Prior cardiac transplantation or prior transplant of other organ (lung, liver, other).
  3. Prior cardiac surgery and/or percutaneous cardiac intervention for arteriothrombotic complications, or valvuloplasty.
  4. Presence or requirement of a Left Ventricular Assisted Device (LVAD).
  5. History of intracardiac thrombosis or arteriothromboembolic events including stroke or transient ischemic attack (TIA).
  6. Left ventricular ejection fraction (LVEF) <40% at baseline.
  7. History of the following prior arteriothromboembolic complications: myocardial infarction or unstable angina.
  8. Significant (greater than moderate) valvular stenosis or regurgitation on echocardiogram.
  9. Requires mechanical ventilation.
  10. Anti-AAV9 neutralizing antibody titer >1:40.
  11. Concurrent enrollment in any other clinical investigation involving use of an investigational agent for the treatment of CHF or cardiomyopathy.
  12. Active hepatitis B or C infection (including patients with positive hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B core antibody (HBcAb), or detectable hepatitis B virus (HBV) or hepatitis C virus (HCV) viral load). Patients with previous, adequately resolved HBV or HCV are eligible.
  13. Significant medical conditions including documented human immunodeficiency virus (HIV) infection, active viral or other hepatitis, poorly-controlled hypertension or diabetes, poorly controlled cardiac arrhythmia, or uncontrolled viral, bacterial, or fungal infection.
  14. Any concomitant medical or psychiatric condition that in the opinion of the Investigator renders the patient unfit for study participation or at higher than acceptable risk for study participation.
  15. Active hematologic or solid organ malignancy, not including non-melanoma skin cancer or other carcinoma in situ. Patients with previously resected solid organ malignancies or definitively treated hematologic malignancies may be eligible if there has been no evidence of active malignancy during the prior 3 years.
  16. Any contraindication to use of sirolimus which includes hypersensitivity to sirolimus or HC-60 (polyoxyl 60 hydrogenated castor oil).
  17. Active or latent tuberculosis.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Colorado

    Aurora, Colorado, 80045

  • University of California, San Diego

    La Jolla, California, 92037

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: A Clinical Study Evaluating a Recombinant Adeno-Associated Virus Serotype 9 (rAAV9) Capsid Containing the Human Lysosome-Associated Membrane Protein 2 Isoform B (LAMP2B) Transgene (RP-A501; AAV9.LAMP2B) in Male Patients With DD

This is a non-randomized open-label Phase 1 study to evaluate the safety and toxicity of gene therapy using a recombinant adeno-associated virus serotype 9 (AAV9) containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).

Read the detailed description

The study is a non-randomized open-label Phase I clinical trial to characterize the safety and toxicity associated with infusion of a recombinant adeno-associated serotype 9 (rAAV9) capsid containing the human lysosome-associated membrane protein 2 isoform B (LAMP2B) transgene (investigational product (IP), RP-A501) in male patients with Danon Disease (DD).

During the course of the study, approximately 7-10 male subjects age 8 and over will receive a single intravenous (IV) infusion of the IP. Prior to infusion of IP, rituximab and sirolimus will be administered prophylactically.

All patients are planned to be followed for 36 months after investigational product administration. After the end of the follow-up period, patients will enter a Long-Term Follow-Up (LTFU) study enabling follow-up for an additional 2 to 5 years post-IP administration.

The study will also enable an initial evaluation of whether or not the IP results in cardiomyocyte and skeletal muscle transduction and gene expression and preliminary assessment of the extent of cardiomyocyte and histologic correction. Additionally, a preliminary evaluation of clinical stabilization following infusion will also be made.

Conditions
Danon Disease
Being tested
RP-A501
Keywords
hypertrophic cardiomyopathy, HCM, X-linked disease, LAMP 2A, Pediatric, Skeletal myopathies
Medical subject headings
Glycogen Storage Disease Type IIb, Cardiomyopathy, Hypertrophic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RP-A501Biological

    RP-A501 is a gene therapy product consisting of a rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single IV infusion.

Study groups in NCT03882437
Study groupRoleWhat they receive
RP-A501ExperimentalRP-A501 is a gene therapy product consisting of a rAAV9 capsid containing the human LAMP2B transgene which will be administered as a single intravenous (IV) infusion. Subjects will receive one of three dose levels depending on the cohort.
Receives: Biological: RP-A501

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)

    Evaluation of safety associated with RP-A501

    Measured: 3 years

  2. Number of participants within each dose level cohort with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE)

    Assessment of safety at both doses (single IV administration)

    Measured: 3 years

  3. Evaluation of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy

    Assessment of cardiomyocyte histologic correction following administration of RP-A501 via endomyocardial biopsy

    Measured: 3 years

  4. Preliminary evaluation of clinical stabilization of cardiomyopathy following administration of RP-A501 via cardiopulmonary testing

    Assessment of clinical stabilization of cardiomyopathy following infusion of RP-A501 via cardiopulmonary testing

    Measured: 3 years

Secondary outcomes (5)

  1. Determination of the percentage of patients in whom RP-A501 resulted in a sustained improvement or stabilization in cardiovascular pathophysiology

    Evaluation of sustained improvement or stabilization in cardiovascular pathophysiology as assessed by medical evaluation, radiographic evaluation of cardiac structure and function, and cardiopulmonary exercise/physiologic parameters

    Measured: 3 years

  2. Determination of the percentage of patients in whom cardiomyocytes corrected LAMP2B gene and/or protein

    Evaluation of the percentage of patients in whom cardiomyocytes contain the corrected LAMP2B gene and/or protein and improvement in DD-associated histologic abnormalities and when feasible to quantify the extent of genetic and histologic correction in the myocardium.

    Measured: 3 years

  3. Determination and characterization of immunologic response to RP-A501

    Assessment of potential immunogenicity to the components of the investigational product

    Measured: 3 years

  4. Determination of the percentage of patients who require and/or receive treatment for heart failure following RP-A501

    Assessment of the percentage of patients who require and/or receive subsequent cardiac transplantation, left ventricular assist device (LVAD), implantable cardioverter-defibrillator or pacemaker placement, electrophysiologic ablative procedure for cardiac conduction aberrancy or subsequent hospitalizations for heart failure.

    Measured: 3 years

  5. Evaluation of overall survival

    Assessment of overall survival post RP-A501

    Measured: 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Mar 2019
  2. Study start17 Apr 2019
  3. Primary completion3 Jul 2025
  4. Study completion3 Jul 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
Evaluation of RP-A501 in pediatric patients (ages 8-14) will commence only pending determination of safety in the older (adult and age 15-17) population. In Phase 1, RP-A501 will be investigated in three treatment cohorts, as follows with a single cohort currently recruiting: Cohort 1: Adult and age 15-17: 6.7 × 1013 GC/kg (n=3-4) Cohort 2: Adult and age 15-17: 1.1 × 1014 GC/kg (n=2 \[patients already treated; closed for current enrollment\]) Cohort 1A: Pediatric age 8-14: 6.7 × 1013 GC/kg (n=2-4)
Masking
None (open label)
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03882437
Sponsor's protocol ID
RP-A501-0219
Other IDs
LAMPLIGHT-1
Status last verified
Oct 2026
First submitted
12 Mar 2019
Last updated
6 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Greenberg B, Taylor M, Adler E, Colan S, Ricks D, Yarabe P, Battiprolu P, Shah G, Patel K, Coggins M, Carou-Keenan S, Schwartz JD, Rossano JW. Phase 1 Study of AAV9.LAMP2B Gene Therapy in Danon Disease. N Engl J Med. 2025 Mar 6;392(10):972-983. doi: 10.1056/NEJMoa2412392. Epub 2024 Nov 18.

    PubMed 39556016

  • Grisorio L, Bongianino R, Gianeselli M, Priori SG. Gene therapy for cardiac diseases: methods, challenges, and future directions. Cardiovasc Res. 2024 Nov 25;120(14):1664-1682. doi: 10.1093/cvr/cvae207.

    PubMed 39302117

  • O'Neil EC, Uyhazi KE, O'Connor K, Aleman IA, Pulido JS, Rossano JW, Aleman TS. DANON DISEASE: A MODEL OF PHOTORECEPTOR DEGENERATION SECONDARY TO PRIMARY RETINAL PIGMENT EPITHELIUM DISEASE. Retin Cases Brief Rep. 2022 Nov 1;16(6):707-713. doi: 10.1097/ICB.0000000000001125.

    PubMed 36288619

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing RP-A501 in people with Danon Disease, run by Rocket Pharmaceuticals Inc. at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with treatment-related adverse events as assessed by United States (US) National Cancer Institute Common Terminology Criteria (NCI CTCAE) (time frame: 3 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03882437, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2026.

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